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THE CANCER, DIABETES, AND HEART DISEASE LINK

Research shows
these diseases are interrelated as well as the strategies to prevent and manage
them.

It’s common knowledge that clients and
patients with type 2 diabetes have a higher risk of developing cardiovascular
dis­ease (CVD). But did you know that heart disease can be associ­ated with an
increased risk of type 2 diabetes and that diabetes can raise the risk of
various cancers?

Research has shown there are
interrelationships among type 2 diabetes, heart disease, and cancer. These
interrelation­ships may seem coincidental and based only on the fact these
conditions share common risk factors. However, research sug­gests these
diseases may relate to one another in multiple ways and that nutrition and
lifestyle strategies used to prevent and manage these diseases overlap
considerably.

This continuing education activity will
evaluate the current research showing how cancer, type 2 diabetes, and CVD
inter­relate with one another, and examine how nutrition and physi­cal activity
recommendations

developed to reduce cancer risk intersect and can be used to
care for patients who have or are at risk for diabetes and heart disease.

Interrelated Conditions

Type 2 diabetes has long been known to
increase CVD risk and mortality. Even after adjusting for other heart disease
risk factors, people with type 2 diabetes are at least twice as likely to
develop CVDand face two to four times greater cardiovascular mortality compared
with people without diabetes. Hyperten­sion and dyslipidemia are common in
diabetes, although diabe­tes also seems independently linked to CVD risk.

Certain medications that effectively treat
components of CVD may raise the risk of developing type 2 diabetes or make the
condition more difficult to control. This includes some antihypertensive
medications, such as diuretics and cer­tain beta-blockers, and LDL-lowering
statins. The JUPITER trial (Justification for the Use of Statins in Primary
Prevention: an Intervention Trial Evaluating Rosuvastatin), a randomized
double-blind placebo-controlled study investigating the use of rosuvastatin in
the primary prevention of CVD, shows these medications are most likely to
promote hyperglycemia in people with prediabetes, metabolic syndrome, or
obesity.

Moreover, several meta-analyses have
associated type 2 dia­betes with colon, postmenopausal breast, and pancreatic
can­cers, three of the five leading causes of cancer mortality in the United
States. The risk of liver cancer rises 250% in those with type 2 diabetes13;
the risk of developing endometrial and bladder cancers, and non-Hodgkins
lymphoma also increases.

Among cancer patients, preexisting
diabetes is associated with 30% to more than 70% higher mortality rates. Metfor­min
may decrease cancer risk, and research is under way to examine how various
diabetes treatments affect cancer risk.

Type 2 diabetes generally is
associated with a 25% to 35% decreased risk of prostate cancer. However,
diabetes doesn’t seem to reduce the most aggressive forms of this cancer, and
all-cause mortality rates appear to be higher in those with both prostate
cancer and type 2 diabetes.

In other research, the link between
pancreatic cancer and diabetes is bimodal, since diabetes can be both a result
of and a risk for this type of cancer.

Adult survivors of childhood cancer face
an increased risk of type 2 diabetes and metabolic syndrome. Some of this risk
may be associated with excess body fat or sedentary lifestyles more commonly
seen in this group, but it also seems to involve some independent effect,
particularly among patients treated with radiation therapy. Androgen-deprivation
therapy for prostate cancer often leads to sarcopenic obesity and increases
insulin resistance.

Although cancer survivors may worry most
about recurrent or second cancers, heart disease is the predominant cause of
death in those who have some of the most common cancers. This isn’t just a case
of shared risk factors; certain types of cancer therapy can have cardiotoxic
late effects.

When it comes to the interrelationship
between heart dis­ease and cancer, growing research has shifted focus from
total LDL cholesterol to small-dense LDL as the source of CVD risk. Atherogenic
dyslipidemia, defined by increased small-dense LDL with increased
apolipoprotein B and higher fasting insulin or with elevated serum
triglycerides and decreased HDL cholesterol, has been linked to a significant
rise in coronary heart disease (CHD) risk. This lipid pattern often occurs with
metabolic syndrome, which doubles the risk of CVD38 and also may include
hypertension, increased waist circumference, and elevated fasting blood sugar.
This metabolic environment of insulin resistance and inflammation greatly
overlaps with the metabolic environment in which several types of cancers may
develop and flourish.

Understanding the Cancer Link

Research has found that cancer, type 2
diabetes, and CVD have common physiological associations. These associations
partially overlap with one another and all remain active areas of research.

Obesity

Adipose tissue consists of adipocytes and
infiltrating mac­rophage cells of the immune system. Greater body fat, particu­larly
with insulin resistance, tends to increase the production of the hormone
leptin, a mediator that regulates energy balance. Rising leptin tends to
further increase hyperinsulinemia, pro­mote inflammation, and induce aromatase
enzymes that raise estrogen production in postmenopausal women. Emerging labo­ratory
studies suggest leptin also may directly promote cancer cell growth. Moreover,
greater body fat is linked with decreased production of adiponectin, a
protective anti-inflammatory hor­mone. In postmenopausal women, body fat
becomes the primary site of estrogen synthesis, and obesity is linked with
substantial increases in bioavailable estrogen.

Adipose tissue secretes cytokines such as
tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). These
cytokines can promote the inflammation, insulin resistance, and endothelial
dysfunction now linked with type 2 diabetes and coronary artery disease (CAD)
as well as promote cancer development by increasing cell proliferation and
decreasing apoptosis.

Hyperinsulinemia and Insulin Resistance

Hyperinsulinemia stemming from insulin
resistance may exist for many years before a diabetes diagnosis, and it has
wide-ranging effects. Normally, when insulin binds to its receptors, it
activates two pathways: the metabolic pathway and the mitogenic pathway. Insulin
resistance inhibits the metabolic pathway, which is the pathway that increases
trans­port of glucose into cells, promotes glycogen synthesis, and suppresses
liver gluconeogenesis. Without insulin’s normal postprandial inhibition of
lipolysis, circulating free fatty acid levels—fundamental to the pathogenesis
of insulin resis­tance—and liver triglyceride production rise, which
contributes to atherogenic dyslipidemia.

Inflammation is an inherent part of
atherosclerotic plaque development, and it seems to contribute to insulin
resistance. Exposure to free radicals produced in the body and externally can
damage cell DNA through oxidation and strand breaks, and interfere with DNA
repair. The genetic mutations that result can lead to cancer. Chronic,
low-grade inflammation can result from DNA damage and create an environment in
which more damage occurs. IL-6 and TNF-alpha, for example, promote cancer
progression through several pathways.

Hyperglycemia

One of the unanswered questions about the
link among cancer, type 2 diabetes, and CVD involves the effect of elevated
blood glucose. Hyperglycemia is associated with increased free radical
formation and may lead to the development of advanced glycation end products
(AGEs), or proteins or lipids that become glycated after exposure to sugars
that can increase inflamma­tion. Some laboratory studies suggest higher
circulating glu­cose may support malignant cell growth.

Some prospective cohort and case-control
studies link ele­vated hemoglobin A1c and other measures of hyperglycemia with
an increased risk of colorectal, pancreatic, endometrial, and other cancers. However,
these studies often don’t con­trol for insulin levels or potential confounders,
such as exog­enous insulin, sulfonylureas, or metformin used for diabetes
treatment. A meta-analysis of intervention trials of people with type 2
diabetes shows no association between hemoglobin A1c and cancer risk or cancer
mortality.

Intersection of Recommendations

Research is clear that the key to reducing
the risk of devel­oping type 2 diabetes, cancer, and CVD is to reduce excess
body fat, especially around the waist. Reduction of excess body fat is a
primary target for reducing cancer risk, just as it is for type 2 diabetes,
prediabetes, and CVD.

In the Diabetes Prevention Program and
Look AHEAD (Action for Health in Diabetes) trials, even modest weight loss was
linked to clinically significant improvements in multiple health metrics, such
as subclinical inflammation (measured by C-reactive protein), blood sugar,
blood pressure, triglycerides, and HDL cholesterol. The most recent standards
from the American Diabetes Association (ADA) recommend that individ­uals who
are overweight or obese lose 7% of their body weight.

Excess body fat increases the risk of
colon, postmenopausal breast, endometrial, kidney, esophageal, and pancreatic
can­cers, and probably gallbladder cancer. To reduce cancer risk, the American
Institute for Cancer Research (AICR) and the American Cancer Society (ACS)
recommend being as lean as possible while avoiding underweight.

Studies show the lowest cancer mortality
rates in those at the lower end of the normal BMI range. For people who are
already obese or significantly overweight, even modest weight loss is likely
beneficial. Regardless of BMI, people with elevated body fat can have increased
insulin resistance, inflammation, and metabolic syndrome. In fact, CVD
mortality is significantly higher in these women.

Abdominal fat particularly is linked with
insulin resistance and elevated levels of inflammatory cytokines. Moreover, the
combination of greater waist size and elevated triglyc­erides independently
predicts CAD in men and women, and increases in waist circumference are
directly linked with greater colon cancer risk.

The 40-inch and 35-inch waist
circumference standards from the National Institutes of Health, used to define
metabolic syndrome58 in men and women, respectively, may not be sensi­tive
enough to identify many people at risk of health problems related to excess
body fat. So the AICR Expert Report recom­mends the World Health Organization
limits, which call for waists to be no larger than 37 inches in men and 31.5
inches in women. These standards also are better predictors of type 2 diabetes
and cardiometabolic risk.Further research is needed for standards that reflect
ethnicity-based differences in body fat deposition.

Weight-Control Strategies

Weight-management recommendations from the
AICR and the ACS include limiting high-calorie foods and beverages, getting
regular physical activity, and choosing appropriate portion sizes.

AICR recommendations also encourage people
to limit calorie-dense foods. Decreasing calorie density can reduce calorie
consumption. This fits well with eating patterns linked with a lower risk of
cancer, diabetes, and CVD. For example, one of the primary ways to lower
calorie density is to increase vegetable consumption.

Research suggests foods low in calories
should be substi­tuted for foods high in calories rather than simply added to
the diet. The goal of an overall eating pattern low in calorie density doesn’t
exclude modest amounts of foods high in calorie den­sity, such as oils, nuts,
and seeds, which add nutritional value.

Physical Activity

Regular exercise is key to reducing the
risk of and control­ling type 2 diabetes and CVD, and is linked with lower
cancer risk, especially colorectal, endometrial, and postmenopausal breast.
Recommendations for physical activity to lower cancer risk are similar to those
promoted for overall health, which include a minimum of 30 minutes of moderate
activity daily, and preferably 60 minutes of moderate or 30 minutes of vigorous
activity daily.

Emerging research suggests that aside from
the time indi­viduals spend exercising, limiting the amount of time they’re
inactive provides yet another means of improving biomark­ers of cardiovascular
health, reducing insulin resistance, and likely lowering cancer risk. Research
shows that inter­spersing short bouts of light exercise within periods of seden­tary
activity seems beneficial to glucose and fat metabolism and waist size.

Although one of the expected
benefits of regular exercise is maintaining a healthy weight, physical activity
can benefi­cially affect abdominal fat, insulin resistance, and estrogen
levels, and increase HDL cholesterol without weight loss. Because direct
effects of exercise on insulin last 24 to 72 hours, it’s best to go no more Vegetables, Fruits, Whole Grains, and Beans

Just as vital as physical activity for the
reduction of type 2 diabetes, cancer, and CVD are the types and variety of
foods individuals eat. Plant foods are encouraged because they supply dietary
fiber, nutrients, and phytochemicals that seem to impact the process of cancer
development.

Dietary fiber is associated with lower
colorectal cancer risk, and a meta-analysis links dietary fiber with reduced
breast cancer risk. The current dietary fiber recommendation for people with
diabetes is no different from that of the general public: 14 g/1,000 kcal, with
higher amounts possibly beneficial.

It isn’t clear, however, whether some of
the health benefits seen in studies of people with high fiber consumption come from
other qualities of foods high in fiber. The choice of whole grains vs. refined
grains provides an example of this. Analysis in the AICR/WCRF (World Cancer
Research Fund) continuous update project shows a reduction in colorectal cancer
linked to cereal fiber. Yet reduced colorectal cancer risk associated with
whole grains may come from more than fiber alone, since whole grains are higher
than refined grains in several nutrients and provide antioxidant phytochemicals
such as polyphenols.

Legumes are a concentrated source of
dietary fiber. They also provide significant amounts of resistant starch and
flavo­noid phytochemicals that may function as antioxidants and have
cancer-inhibitory effects.

Vegetables and fruits are important
because they’re low in calorie density and likely contribute directly to
reducing cancer risk. Besides fiber, they provide nutrients vital for DNA
production and immune function. What’s more, research is only beginning to
reveal the role of phytochemicals in produce. Many are antioxidants and, at
least in laboratory studies, they have the potential to reduce cancer
development. For example, allyl sulfur compounds in garlic and onion, and
isothiocyanates formed from compounds in cruciferous vegetables may promote
epigenetic changes that activate tumor suppressor genes.

Dietary Recommendations

Because of the cancer-fighting compounds
found in fruits, vegetables, and whole grains, the AICR recommends at least
two-thirds of the food individuals eat come from plants.

The 2010 Dietary Guidelines for Americans
say at least one-half of grain products should be whole grain, and people
should aim for at least three servings per day. Yet recent reviews that focus
on decreasing insulin resistance and ACS recommen­dations concur with the AICR’s
advice to eat more than three servings per day of whole grains if possible and
“minimize con­sumption of refined grains.”

For greater health benefits, clients can
use dried beans and peas in place of all or part of the meat in some dishes.
When it comes to fruits and vegetables, research shows individuals can eat
smaller amounts than what’s recommended to reduce heart disease and still lower
cancer risk. ACS recommenda­tions call for a total of at least 21⁄2 cups of
vegetables and fruits daily. The AICR recommends at least five standard-size
serv­ings daily of nonstarchy vegetables and fruits, which means potatoes and
legumes don’t count toward the total.

Fruit and vegetable targets should focus
not only on the amount but also on a variety of choices. To help control or
decrease hypertension risk, dietitians can suggest clients include choices rich
in potassium. To reduce cancer risk, vari­ety also refers to selections rich in
carotenoids and vitamin C as well as cruciferous vegetables, garlic-onion
family vegetables, and berries, among other foods.

Limiting Red Meat

In addition to eating more plant foods,
limiting red meat consumption also is important. Heart-health messages usually
focus on saturated fat and group together poultry, seafood, and lean cuts of
red meat as recommended choices. However, research on cancer suggests these
foods aren’t all the same.

A meta-analysis conducted as part of the
AICR/WCRF con­tinuous update project shows a 17% increased risk of colorectal
cancer per 100 g of red meat eaten daily. Its higher heme iron content may
increase risk by promoting nitrosamine formation within the gut as well as
through the generation of DNA-damaging free radicals.

Processed meats—those preserved by
smoking, curing, salting, or preservatives—are linked to increased colorectal
cancer risk, showing an 18% higher risk for each 50 g consumed per day.76 Most
processed meats are high in sodium, so limiting them already is a boon for
heart health. A meta-analysis links about 2 oz of daily processed meat
consumption with a 42% rise in CHD and also a 19% increase in diabetes risk.

Clients can reduce their meat consumption
through several different approaches, all of which fit well with other
prevention-focused goals, such as the following:

• The AICR recommends individuals eat no
more than 18 oz (cooked weight) of red meat per week, which includes beef,
lamb, and pork.

• Substitute vegetables and beans for some
or all of the red and processed meat in dishes, which supports the goals of
increasing plant foods and decreasing calorie density.

• The American Heart Association (AHA)
recommends eating at least 8 oz, or two servings, of fish each week.

Curb High-Sodium Foods

Sodium intake is another concern. The 2010
Dietary Guide­lines call for keeping daily sodium consumption below 2,300 mg.
However, about one-half of the US population falls into groups whose blood
pressure tends to be especially sodium sensi­tive and are therefore advised to
reduce sodium to 1,500 mg per day. This includes people aged 51 and older, and
those of any age who are African American or have hypertension, diabetes, or
chronic kidney disease.

Although sodium targets for cardiovascular
health are lower than needed to decrease cancer risk, consumption of salt and
salt-preserved foods is linked to an increased risk of stomach cancer.

Limiting sodium may make dietary
strategies seem more complex, but it can support a healthful eating pattern if
the medical community does the following:

• Pairs messages about limiting salt with
suggestions for using herbs, spices, garlic, and other flavorings. People will
be able to enjoy flavorful food and get health-protective phy­tochemicals into
their diets.

• Teaches people how to replace
high-sodium convenience foods with whole foods, which often are lower in
saturated and trans fats and added sugar.

Alcohol Consumption

Alcohol in moderation is strongly linked
to a decreased risk of CHD, possibly related to increased HDL cholesterol,
reduced inflammation, and lower fibrinogen, a protein essential for blood
clotting that when too high is a marker of increased CVD risk. In moderation,
alcohol decreases insulin resistance and type 2 diabetes risk. However, alcohol
in excess can raise triglycerides and boost the risk of developing hypertension
and diabetes.

Many people are unaware that alcohol is
linked to an increased risk of colon cancer in men, pre- and postmeno­pausal
breast cancer, and mouth and throat cancers.

According to the AHA, “Consumption of
alcohol cannot be recommended solely for CVD risk reduction.”

For people who choose to drink alcohol,
the unified recom­mendation from the AICR, the ACS, the AHA, and the ADA is to
limit alcoholic drinks to two per day for men and one per day for women. Women
need to consume fewer than one drink per day to reduce their breast cancer risk
to that of nondrinkers, so they will need help making choices based on their
individual health risks and lifestyle preferences.

Due to the trends in increased portion
sizes, the healthcare community must clearly define what’s meant by one drink:
5 oz of wine, 12 oz of beer, or 11⁄2 oz of 80-proof liquor.

Weaving Recommendations Into Healthful Eating Patterns

Research increasingly is looking beyond
the health impact of individual food choices to how combined choices as part of
overall eating patterns impact diabetes, heart disease, and cancer. Sometimes
individual studies compare a particular eating pattern to the Western diet and
show a reduced risk of one or more of these conditions. Such comparisons don’t
show that the particular alternative-eating pattern tested is “the best” choice
for everyone.

Research is exploring how genetic
polymorphisms may affect response to dietary fat, carbohydrate, and protein
intake and certain cancer-protective phytochemicals. Meanwhile, the challenge
is to help people follow healthful eating patterns that satisfy their unique
food preferences, calorie needs, health issues, and lifestyles.

Healthful food choices can be combined
into different pre­dominantly plant-based eating patterns, including a
vegetarian diet, Dietary Approaches to Stop Hypertension (DASH), and the
Mediterranean diet.

Very low-fat vegetarian eating patterns include
the lacto-ovo vegetarian approach Dean Ornish, MD, originally took to help
reverse atherosclerotic heart disease. He has since shown decreases in
inflammation markers and endothelial dysfunc­tion with this approach in a small
group of men with CAD or CAD risk factors8 and protective changes in prostate
cancer gene expression and decreased prostate-specific antigen among men with
low-risk prostate cancer with a very low-fat vegan diet.

These eating patterns keep fat and
carbohydrate intake to 10% and 75% of total calories, respectively. Total fat
intake is very low, avoiding even fats in nuts and oils often considered
healthful. Despite the high carbohydrate content, hemoglobin A1c levels have
been reduced. However, these diets’ effects as reported in these studies can’t
be separated from other com­ponents that promote health, such as three hours
per week of moderate physical activity, smoking cessation, one hour of stress
management daily, and active group support.

The 2010 Dietary Guidelines support
following the DASH diet, which was originally developed to prevent or control
hyper­tension. It decreases LDL cholesterol and blood pressure, and some
research suggests it can decrease inflammation and hemoglobin A1c levels in
people with type 2 diabetes. Limited research links scores showing how closely
the DASH diet was followed with reduced risk of colorectal and estrogen
receptor-negative breast cancer and type 2 diabetes.

An eating pattern such as the DASH diet is
low in total and sat­urated fat but does include limited amounts of oil. It’s
high in veg­etables, fruits, and grains (with at least three servings of whole
grains per day) and includes low- or nonfat dairy daily, beans and nuts often,
and substantially limited sweets and sodium. (Details of how the proportions of
different food groups are combined in the DASH diet are provided in Appendix 10
of the 2010 Dietary Guidelines report.) The DASH diet emphasizes vegetables and
fruits, so it generally increases an individual’s intake of potas­sium and
dietary fiber, and reduces sodium intake.

Moreover, the DASH diet is relatively high
in carbohydrate. Results of the OmniHeart intervention trial suggest that, at
least for some people and in the short-term, replacing some carbohydrate with
plant proteins or unsaturated fat may pro­duce even greater improvements in
blood pressure and ath­erogenic lipoproteins,89,90 molecules that transport
cholesterol in the bloodstream that can cause blood vessel blockages and lead
to heart attacks and strokes.

The 2010 Dietary Guidelines advisory panel
also high­lights the Mediterranean eating pattern as a healthful choice. It’s a
plant-based diet that includes an abundance of vegetables, fruits, grains, and
beans. The Mediterra­nean eating pattern isn’t necessarily low in total fat,
but most of the fat comes from olive oil and nuts, so saturated fat is below
10% of total calories. Research links this eating pattern with decreases in
metabolic syndrome and in car­diovascular and cancer mortality. Glucose control
and insulin resistance also may improve.

Because many people think of low-fat
eating as a key to health, clinical trials comparing the Mediterranean diet
with a low-fat diet are of particular interest. In the PREDIMED dietary
intervention trial, people assigned to a Mediterranean-type eating pattern were
less likely to develop diabetes or metabolic syndrome than those eating a
low-fat diet, and showed lower levels of the oxidized form of LDL now
considered an essential influence in atherosclerosis. A meta-analysis that
compared the Mediterranean diet with low-fat eating in overweight adults linked
this eating pattern with lower levels of metabolic syn­drome components,
including blood pressure and fasting glu­cose, and reduced levels of
high-sensitivity C-reactive protein, a marker of inflammation.

Weight management is a major goal for
lowering the risk of and controlling type 2 diabetes, heart disease, and
cancer. The Mediterranean diet shows how a diet containing plenty of veg­etables
and a higher percentage of calories from fat still can have moderately low
calorie density and support weight goals.

Paradigm Shift

Research increasingly shows that the risk
of and damage from type 2 diabetes, CVD, and cancer is associated with a
constellation of insulin resistance, inflammation, cell signal­ing and
epigenetic changes, and hormones. As health profes­sionals specialize and
become more problem focused, it can be easy to concentrate on single measures,
such as hemoglo­bin A1c or LDL levels, and miss the big picture. This big
picture extends beyond an intersection of heart disease and diabetes, and
includes cancer as well.

Avoiding tobacco is vital to reducing the
risk of all three dis­eases and promoting overall health. However, lifestyle
matters to nonsmokers, too. Among almost 112,000 nonsmoking men and women in
the Cancer Prevention Study-II Nutrition Cohort, all-cause mortality—reflecting
fewer deaths because of both heart disease and cancer—was 42% lower with weight
control, regular physical activity, limited use of alcohol, and a health­ful
diet limited in red and processed meats, and focused around whole plant foods.

The Nutrition Professional’s Role

What does this mean for nutrition care?
Dietitians have more reason than ever to encourage nutrition interventions
focused on preventive health and act early in response to undesirable metabolic
changes in their clients and patients. When these individuals are faced with
prediabetes or prehypertension, they may think trouble doesn’t start until
later, but that’s not the case. By reframing this as a metabolic environment
condu­cive to heart disease and cancer development, nutrition pro­fessionals
will be better able to help clients and patients make changes sooner rather
than later.

Strong evidence shows that one of the most
effective steps to reducing cancer risk and addressing the metabolic abnor­malities
of the diabetes-CVD-cancer connection is to reach and maintain a healthful
level of body fat. Since research doesn’t clearly show more protection from one
type of healthful eating pattern than another, dietitians need to help people
shift their focus from what diet is best to identify changes they can make to
alter the balance of calories expended and consumed.

The health impact of eating patterns
requires more than cal­culating percentages of fat grams, protein, or
carbohydrate; it involves the specific food choices behind those numbers. For
example, the type of grain products and animal proteins chosen, and both the
amount and variety of vegetables and fruits are all pieces in this puzzle.

As the word spreads about how heart
disease, diabe­tes, and cancer risk are interrelated, it will be imperative for
nutrition professionals to learn the steps necessary to help clients and patients
lower risk. These steps are both evi­dence based and compatible with overall
nutrition strategies. By showing people eating patterns with multiple health
ben­efits and referring them to reliable sources of information, dietitians can
provide important support for their clients’ and patients’ overall health.

— Karen Collins, MS, RD, CDN, is
nutrition advisor to the American Institute for Cancer Research. She promotes
healthful eating as a speaker, consultant, and syndicated columnist, and
through her blog Smart Bytes®